This invention relates to healing wounds.
Growth factors are polypeptide hormones which stimulate a defined population of target cells. Examples of growth factors include platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-I), transforming growth factor beta (TGF-.beta.), transforming growth factor alpha (TGF-.alpha.), epidermal growth factor (EGF), and fibroblast growth factor (FGF).
TGF-.beta. is a multifunctional regulatory polypeptide synthesized by many cell types and sequestered in human platelets in amounts similar to PDGF. The in vitro biological effects of TGF-.beta. are dependent upon the presence of other growth factors: TGF-.beta. in the presence of PDGF stimulates fibroblast growth, and in the presence of EGF inhibits fibroblasts (Roberts, et al. Proc. Natl. Acad. Sci, USA 82:119). TGF-.beta. inhibits proliferation of epithelial cells in vitro (Shipley et al., 1986, Cancer Res. 46:2068), and in vivo stimulates DNA, total protein, and collegen synthesis when injected into wound chambers (Sporn et al., 1986, Science 219:1329). The breaking strength of incisional wounds increases in a dose dependent manner after application of TGF-.beta. (Mustoe, et al., Science 237:1333).
IGF-I is synthesized de novo in the liver and secreted into the plasma. In vitro, IGF-I can promote DNA synthesis in both mesenchymal and epithelial cells (Van Wyk 1984, Hormonal Proteins and Peptides, Li, ed.). Addition of IGF-I in vivo by itself does not promote wound healing, but when added with PDGF the combination stimulates connective tissue and epithelial and bone cell proliferation (Lynch, et al., 1987, Proc. Natl. Acad. Sci., USA 84:7696, Lynch et al., 1987, J. Clin. Periodontol. 16:545).